The transient receptor potential ankyrin repeat 1 (TRPA1) channel is believed to be involved in many forms of acute and chronic hyperalgesia. Nerve Growth Factor (NGF) regulates chronic inflammatory hyperalgesia by controlling gene expression in sensory neurons, including genes involved in inflammatory hyperalgesia in the dental pulp. We hypothesized that NGF increases functional activities of the TRPA1 channel in trigeminal ganglion neurons. Here, we show that NGF induced a concentration- and time-dependent up-regulation of TRPA1 mRNA in trigeminal ganglia neurons, as detected by real-time RT-PCR and in situ hybridization. In addition, NGF evoked a time-dependent increase of mustard oil (MO)-evoked TRPA1 activation in trigeminal ganglia neurons. Collectively, these findings demonstrate that NGF participates in the functional up-regulation of TRPA1 in trigeminal ganglia neurons. These enhanced activities of TRPA1 could play an important role in the development of hyperalgesia following nerve injury and inflammation in the orofacial region.
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References
1.
Amann R, Sirinathsinghji DJ, Donnerer J, Liebmann I, Schuligoi R (1996). Stimulation by nerve growth factor of neuropeptide synthesis in the adult rat in vivo: bilateral response to unilateral intraplantar injections. Neurosci Lett203:171–174.
2.
Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, et al. (2004). Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron41:849–857.
3.
Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Hogestatt ED, et al. (2005). Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci USA102:12248–12252.
4.
Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, et al. (2006). TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell124:1269–1282.
5.
Bowles WR, Sabino M, Harding-Rose C, Hargreaves KM (2004). Nerve growth factor treatment enhances release of immunoreactive calcitonin gene-related peptide but not substance P from spinal dorsal horn slices in rats. Neurosci Lett363:239–242.
6.
Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999). A capsaicin-receptor homologue with a high threshold for noxious heat. Nature398:436–441.
7.
Chichorro JG, Lorenzetti BB, Zampronio AR (2004). Involvement of bradykinin, cytokines, sympathetic amines and prostaglandins in formalin-induced orofacial nociception in rats. Br J Pharmacol141:1175–1184.
8.
Chichorro JG, Zampronio AR, Souza GE, Rae GA (2006). Orofacial cold hyperalgesia due to infraorbital nerve constriction injury in rats: reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs. Pain123:64–74.
9.
Chomczynski P, Sacchi N (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem162:156–159.
10.
Diogenes A, Patwardhan AM, Jeske NA, Ruparel NB, Goffin V, Akopian AN, et al. (2006). Prolactin modulates TRPV1 in female rat trigeminal sensory neurons. J Neurosci26:8126–8136.
11.
Eide PK, Rabben T (1998). Trigeminal neuropathic pain: pathophysiological mechanisms examined by quantitative assessment of abnormal pain and sensory perception. Neurosurgery43:1103–1110.
12.
Heese K, Hock C, Otten U (1998). Inflammatory signals induce neurotrophin expression in human microglial cells. J Neurochem70:699–707.
13.
Hille B (2001). Ion channels of excitable membranes. 3rd ed. Sunderland, MA: Sinauer Associates Inc.
14.
Inaishi Y, Kashihara Y, Sakaguchi M, Nawa H, Kuno M (1992). Cooperative regulation of calcitonin gene-related peptide levels in rat sensory neurons via their central and peripheral processes. J Neurosci12:518–524.
15.
Jeske NA, Patwardhan AM, Gamper N, Price TJ, Akopian AN, Hargreaves KM (2006). Cannabinoid WIN 55,212–2 regulates TRPV1 phosphorylation in sensory neurons. J Biol Chem281:32879–32890.
16.
Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, et al. (2004). Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature427:260–265.
17.
Katsura H, Obata K, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, et al. (2006). Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp Neurol200:112–123.
18.
Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, et al. (2006). TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron50:277–289.
19.
Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S, Aloe L, et al. (1994). Mast cells synthesize, store, and release nerve growth factor. Proc Natl Acad Sci USA91:3739–3743.
Manni L, Lundeberg T, Fiorito S, Bonini S, Vigneti E, Aloe L (2003). Nerve growth factor release by human synovial fibroblasts prior to and following exposure to tumor necrosis factor-alpha, interleukin-1 beta and cholecystokinin-8: the possible role of NGF in the inflammatory response. Clin Exp Rheumatol21:617–624.
22.
Obata K, Katsura H, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, et al. (2005). TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury. J Clin Invest115:2393–2401.
23.
Park CK, Kim MS, Fang Z, Li HY, Jung SJ, Choi SY, et al. (2006). Functional expression of thermo-transient receptor potential channels in dental primary afferent neurons: implication for tooth pain. J Biol Chem281:17304–17311.
24.
Patwardhan AM, Berg KA, Akopain AN, Jeske NA, Gamper N, Clarke WP, et al. (2005). Bradykinin-induced functional competence and trafficking of the delta-opioid receptor in trigeminal nociceptors. J Neurosci25:8825–8832.
25.
Patwardhan AM, Jeske NA, Price TJ, Gamper N, Akopian AN, Hargreaves KM (2006). The cannabinoid WIN 55,212–2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc Natl Acad Sci USA103:11393–11398.
26.
Price TJ, Louria MD, Candelario-Soto D, Dussor GO, Jeske NA, Patwardhan AM, et al. (2005). Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF or BDNF: effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion. BMC Neurosci6:4.
27.
Schneider JS, Denaro FJ, Olazabal UE, Leard HO (1981). Stereotaxic atlas of the trigeminal ganglion in rat, cat, and monkey. Brain Res Bull7:93–95.
28.
Sebert ME, Shooter EM (1993). Expression of mRNA for neurotrophic factors and their receptors in the rat dorsal root ganglion and sciatic nerve following nerve injury. J Neurosci Res36:357–367.
Shu XQ, Mendell LM (1999). Neurotrophins and hyperalgesia. Proc Natl Acad Sci USA96:7693–7696.
31.
Skoff AM, Adler JE (2006). Nerve growth factor regulates substance P in adult sensory neurons through both TrkA and p75 receptors. Exp Neurol197:430–436.
32.
Spears R, Dees LA, Sapozhnikov M, Bellinger LL, Hutchins B (2005). Temporal changes in inflammatory mediator concentrations in an adjuvant model of temporomandibular joint inflammation. J Orofac Pain19:34–40.
33.
Steranka LR, Manning DC, DeHaas CJ, Ferkany JW, Borosky SA, Connor JR, et al. (1988). Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions. Proc Natl Acad Sci USA85:3245–3249.
34.
Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, et al. (2003). ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell112:819–829.
35.
Sullins JS, Carnes DL Jr, Kaldestad RN, Wheeler EF (2000). Time course of the increase in trk A expression in trigeminal neurons after tooth injury. J Endod26:88–91.
36.
Wang H, Ehnert C, Brenner GJ, Woolf CJ (2006). Bradykinin and peripheral sensitization. Biol Chem387:11–14.
37.
Wheeler EF, Naftel JP, Pan M, von Bartheld CS, Byers MR (1998). Neurotrophin receptor expression is induced in a subpopulation of trigeminal neurons that label by retrograde transport of NGF or fluoro-gold following tooth injury. Brain Res Mol Brain Res61:23–38.
